Inter- and intratumoral heterogeneity of BCL2 correlates with IgH expression and prognosis in follicular lymphoma
Articolo
Data di Pubblicazione:
2014
Abstract:
Most follicular lymphomas (FLs) are genetically defined by the t(14;18)(q32;q21) translocation that juxtaposes the BCL2 gene
to the immunoglobulin heavy chain (IgH) 3' regulatory regions (IgH-3'RRs). Despite this recurrent translocation, FL cases are
heterogeneous in terms of intratumoral clonal diversity for acquired mutations and variations in the tumor microenvironment. Here
we describe an additional mechanism that contributes to inter- and intratumoral heterogeneity in FLs. By applying a novel singlemolecule
RNA fluorescence-based in situ hybridization (FISH) technique to detect mRNA molecules of BCL2 and IgH in single cells,
we found marked heterogeneity in the number of BCL2 mRNA transcripts within individual lymphoma cells. Moreover, BCL2 mRNA
molecules correlated with IgH mRNA molecules in individual cells both in t(14;18) lymphoma cell lines and in patient samples.
Consistently, a strong correlation between BCL2 and IgH protein levels was found in a series of 205 primary FL cases by flow
cytometry and immunohistochemistry. Inter- and intratumoral heterogeneity of BCL2 expression determined resistance to drugs
commonly used in FL treatment and affected overall survival of FL patients. These data demonstrate that BCL2 and IgH expressions
are heterogeneous and coregulated in t(14;18)-translocated cells, and determine the response to therapy in FL patients.
Tipologia CRIS:
03A-Articolo su Rivista
Keywords:
follicular lymphomas; bcl2; heterogeneity; smFISH; single-molecule RNA FISH; IgH expression
Elenco autori:
A Barreca;C Martinengo;L Annaratone;L Righi;A Chiappella;M Ladetto;A Demurtas;L Chiusa;A Stacchini;N Crosetto;A van Oudenaarden;R Chiarle
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